A variety of past studies have provided insightful, but varied information about the predictors of tumor recurrence, survival, and quality life in patients with head and neck cancer, however, none of the studies have prospectively assessed the nature, relative strength, and interrelationships of these factors together as predictors of recurrence, survival, and quality of life. The specific aims of this study are to test the hypotheses that: 1) health behaviors (smoking and alcohol use), comorbidities, and molecular markers (tumor p53, serum human papilloma virus (HPV-16), and serum vascular endothelial growth factor (VEGF)) are predictors of tumor recurrence; 2)health behaviors, comorbidities, and molecular markers are predictors of survival; 3) health behaviors and comorbidities are predictors of quality of life; and, 4) serum HPV-16 and serum VEGF are sensitive and specific tests for the identification of tumors with high levels of tumor HPV- 16 and tumor VEGF. This observational, longitudinal study will be conducted at three hospitals and enroll 1391 patients. Information on health behaviors, clinical characteristics, treatment modalities, and demographics will be collected through patient surveys and hospital records. Serum will be collected every 3 months for assessment of levels of HPV-16 and VEGF. Tumor tissue will be collected at time of initial tumor biopsy or tumor resection and analyzed for p53, HPV-16, VEGF and for construction of tissue microarrays as a SPORE resource for future molecular epidemiologic studies. Independent variables of interest will include health behaviors, comorbidities, and molecular markers while controlling for tumor site and stage, treatment modalities, and demographic factors. Dependent variables will include 1) tumor recurrence, 2) survival, and 3) quality of life. Stratified and multivariate analyses for cross-sectional and cohort data (e.g. survival data) will then be performed (e.g. Cox proportional hazard models). Newly developed advanced statistical techniques will be used to jointly model the longitudinal biomarkers and survival and tumor recurrence. Advanced techniques for longitudinal data will be used to analyze the quality of life data. The sensitivity and specificity of serum HPV-16 and VEGF will also be calculated in a cohort of patients by correlating each serum marker to its respective tumor marker. The results of this study are expected to directly translate into improvements in detecting tumor recurrence, improving survival, and increasing quality of life for head and neck cancer patients and will provide useful information about screening and prevention services needed by this population.